[Geriatric nephrology: an overview]. / Nefrologia geriatrica: an overview.

INTRODUCTION: Chronic kidney disease (CKD) is a highly prevalent condition and its prevalence is increasing worldwide, particularly in adults aged 70 years. Epidemiological studies showed that as many as 2054% of the older adults suffer from CKD in stages 3-5. Nevertheless the question whether this lower eGFR is a consequence of kidney disease or if it is the result of a physiological aging is still debated, even if it implies a reduced renal reserve and vulnerability to drugs overdose with increased risk of acute kidney injury (AKI). MATERIALS AND METHODS: PubMed search was conducted for available English literature, describing the actual knowledge about specific and frequent issues reported in the acute and chronic kidney disease in older adults. Prospective and retrospective studies, as well as meta-analyses and latest systematic reviews were included. RESULTS: Most of the studies examined and reviewed were discarded for wrong population or intervention or deemed unfit. Only 103 met the inclusion criteria for the review. The studies included in the review were grouped into two areas: chronic and acute kidney disease in older adults and we have analysed the peculiar and frequently found issues in this population. CONCLUSIONS: The geriatric population is increasing worldwide. We should consider peculiar aspects of this population, such as sarcopenia, malnutrition, psychological and cognitive deficits and increased risk of AKI, in order to reach a good quality of life, with improved doctor / patient relationship, a greater adherence to therapy, a reduction in health care costs, and if possible, adequate "end of life", as far as it is approved by the patient and his family. The achievement of these objectives requires an organized work in multidisciplinary teams that evaluate overall the geriatric patient.

Effects of vitamin D3 and paricalcitol on immature cardiomyocytes: a novel role for vitamin D analogs in the prevention of cardiovascular diseases.

Cardiovascular diseases are more prevalent in patients with chronic kidney disease than in the general population and they are considered the leading cause of death in patients with end-stage renal disease. The discovery that vitamin D3 plays a considerable role in cardiovascular protection has led, in recent years, to an increase in the administration of therapies based on the use of this molecule; nevertheless, several studies warned that an excess of vitamin D3 may increase the risk of hypercalcemia and vascular calcifications. In this study we evaluated the effects of vitamin D3, and of its selective analog paricalcitol, on immature cardiomyocytes. Results show that vitamin D3 induces cAMP-mediated cell proliferation and significant intracellular calcification. Paricalcitol, however, induces cell differentiation, morphological modifications in cell shape and size, and no intracellular calcification. Furthermore, vitamin D3 and paricalcitol differently affect cardiomyoblasts responses to acetylcholine treatment. In conclusion, our results demonstrate that the effects of vitamin D3 and paricalcitol on cardiomyoblasts are different and, if these in vitro observations could be extrapolated in vivo, they suggest that paricalcitol has the potential for cardiovascular protection without the risk of inducing intracellular calcification.

[Nephrologist's behaviours and perceptions on sideropenic anemia's diagnosis and treatment for conservative phase nephropatic patient intolerant or not responding to oral iron therapy]. / Approccio clinico del nefrologo alla diagnosi e al trattamento dell'anemia sideropenica in pazienti con CKD non-dialitica.

INTRODUCTION. The objective of this survey was to describe the nephrologists attitude on the diagnosis and treatment of patients with non-dialysis Chronic Kidney Disease (CKD stages 3, 4 and 5), with iron deficiency anemia and no response/intolerance to oral iron therapy. Furthermore, this survey describes the nephrologists view about the impact of lack of anemia correction on patient health, as well as the influence of organization and management of nephrological centers on IV iron management. MATERIALS AND METHODS. 60 nephrologists were interviewed via web by using an interactive simulation that investigates nephrologists clinical and therapeutic approach on 3 different types of patients; subsequently, a questionnaire was administered with in-deeper questions. RESULTS. Regarding the first virtual patient, 64% of nephrologists still choose oral iron, while IV iron was chosen by 16% of them. 36% opted for ESA. For the other two virtual patients the most selected treatments were combinations of oral iron + ESA (42% and 36%) or IV iron + ESA (21% and 38%), respectively. According to what was perceived by nephrologists, issues related to IV iron are: patient discomfort due to frequent hospital transfers for IV administration (50%), inadequate center organization (48%), fear of damaging the venous tree (40%). CONCLUSIONS. Half of the nephrologists stated they are unsatisfied with available iron therapies. Difficult therapy management and restrictions of health structure were identified as barriers to the prescription of IV iron therapy. A smaller number of administrations and less free-iron toxicity are expected from nephrologists from the new iron preparations for the management of iron deficiency in patients not responding/intolerant to oral iron therapy.

Effect of paricalcitol and GcMAF on angiogenesis and human peripheral blood mononuclear cell proliferation and signaling.

BACKGROUND: In addition to its role in calcium homeostasis and bone mineralization, vitamin D is involved in immune defence, cardiovascular function, inflammation and angiogenesis, and these pleiotropic effects are of interested in the treatment of chronic kidney disease. Here we investigated the effects of paricalcitol, a nonhypercalcemic vitamin D analogue, on human peripheral blood mononuclear cell proliferation and signaling, and on angiogenesis. These effects were compared with those of a known inhibitor of angiogenesis pertaining to the vitamin D axis, the vitamin D-binding protein-derived Gc-macrophage activating factor (GcMAF). METHODS: Since the effects of vitamin D receptor agonists are associated with polymorphisms of the gene coding for the receptor, we measured the effects of both compounds on mononuclear cells harvested from subjects harboring different BsmI polymorphisms. RESULTS: Paricalcitol inhibited mononuclear cell viability with the bb genotype showing the highest effect. GcMAF, on the contrary, stimulated cell proliferation, with the bb genotype showing the highest stimulatory effect. Both compounds stimulated 3'-5'-cyclic adenosine monophosphate formation in mononuclear cells with the highest effect on the bb genotype. Paricalcitol and GcMAF inhibited the angiogenesis induced by proinflammatory prostaglandin E1. CONCLUSIONS: Polymorphisms of the vitamin D receptor gene, known to be associated with the highest responses to vitamin D receptor agonists, are also associated with the highest responses to GcMAF. These results highlight the role of the vitamin D axis in chronic kidney disease, an axis which includes vitamin D, its receptor and vitamin D-binding protein-derived GcMAF.

Short-term high-dose atorvastatin for periprocedural myocardial infarction prevention in patients with renal dysfunction.

OBJECTIVES: Short-term high-dose atorvastatin administered before percutaneous coronary intervention (PCI) reduces the rate of periprocedural myocardial infarction (pMI) in high-risk patients, such as those with acute coronary syndromes and those with elevated high-sensitivity C-reactive protein. It is unknown whether short-term high-dose administration reduces the rate of pMI in patients with chronic kidney disease. Recently, we observed that in 304 patients with estimated creatinine clearance less than 60 ml/min randomized to receive 80 mg/day of atorvastatin or placebo for 48 h before elective coronary angiography and/or angioplasty, statin administration did not reduce contrast-induced nephropathy (CIN). In this post-hoc analysis, we evaluate the pMI in the subgroup of 161 patients who underwent PCI. METHODS: In all patients, creatine kinase myocardial isoenzyme (CK-MB) [upper reference limit (URL) 5 ng/ml] was assessed before and at 12 and 24 h after PCI. The pMI, defined as CK-MB elevation more than three times the URL, occurred in 27 (17%) patients. RESULTS: The incidence of pMI was 10.4% (of 77 patients) in the atorvastatin and 23% (of 84 patients) in the placebo group (P < 0.05). Multivariate analysis identified the pretreatment with high-dose atorvastatin as an independent predictor of reduced risk of pMI [odds ratio 0.39, 95% confidence interval 0.16-0.96, P < 0.05]. CONCLUSION: This post-hoc analysis shows that short-term high-dose atorvastatin administration reduced pMI in patients with renal dysfunction submitted to elective PCI, but without benefit regarding CIN prevention.

Usefulness of atorvastatin (80 mg) in prevention of contrast-induced nephropathy in patients with chronic renal disease.

We investigated the efficacy of short-term high-dose atorvastatin in decreasing the risk of contrast-induced nephropathy (CIN) in patients with chronic kidney disease (CKD) subjected to coronary angiography and/or angioplasty. CIN occurs in up to 15% of patients with pre-existing CKD and affects clinical outcome. The protective effect of statin therapy against CIN is still controversial. A prospective, single-center study of 304 patients with baseline estimated creatinine clearance <60 ml/min were randomized to receive atorvastatin 80 mg/day or placebo for 48 hours before and 48 hours after contrast medium administration. All patients received intravenous saline hydration and oral N-acetylcysteine 1,200 mg 2 times/day. Iso-osmolar contrast medium was used. CIN was defined as an absolute increase of serum creatinine > or = 0.5 mg/dl within 5 days after the procedure. CIN occurred in 31 patients (10%), 16 (11%) in the placebo group and 15 (10%) in the atorvastatin group (p = 0.86). Mean increase in creatinine was not significantly different in the 2 groups (0.59 + or - 0.17 in placebo group vs 0.72 + or - 0.26 mg/dl in atorvastatin group, p = 0.31). Persistent kidney injury, defined as 1-month increase from baseline creatinine value > or = 25%, was observed in 30% in the placebo group and in 31% in the atorvastatin group (p = 0.58). In conclusion, a short-term administration of high doses of atorvastatin before and after contrast exposure, in addition to standard intravenous hydration and oral N-acetylcysteine, does not decrease CIN occurrence in patients with pre-existing CKD.

Vitamin D receptor alleles and C-reactive protein in hemodialysis patients.

Cardiovascular disease due to atherosclerosis is the major determinant of morbidity and mortality in uremic patients. Inflammation is essential in the development of atherosclerosis and markers of inflammation, in particular C-reactive protein, predict the cardiovascular risk. Vitamin D exerts its effects through the Vitamin D Receptor, coded for by a gene showing several polymorphisms associated with a variety of diseases and differential responses to Vitamin D. We evaluated the association between four Vitamin D Receptor polymorphisms (i.e. those identified by the restriction enzymes BsmI, ApaI, TaqI and FokI) and serum level of C-reactive protein in 88 hemodialysis patients routinely treated with active Vitamin D (calcitriol). Absence or presence of the BsmI, ApaI, TaqI, and FokI restriction sites were denominated B and b, A and a, T and t, F and f respectively. Our results show that the b, a, T, alleles were more frequent in patients with elevated serum level of C-reactive protein compared with patients with normal C-reactive protein level. The differences were statistically significant (p < 0.05). These results suggest that the Vitamin D Receptor alleles b, a, T could be considered novel risk factors in the pathogenesis of inflammation-related, atherosclerosis-dependent cardiovascular disease risk in uremic patients.

A king-size dialysis bed: a couple on hemodialysis for more than 30 years.

Dialysis patients exhibit a higher morbidity and mortality rate than those in the general population of comparable age. Survival on dialysis has become significantly longer and is mainly related to comorbid factors. Patients are usually the main research subjects, but caregivers play a pivotal role in patients' well-being. Here we describe the remarkable case of wife and husband both on hemodialysis for 32 years.

Iron indices and vitamin D receptor polymorphisms in hemodialysis patients.

Cardiovascular disease caused by accelerated atherosclerosis is the major determinant of morbidity and mortality in chronic kidney disease patients. Vitamin D and its analogs provide survival benefit for hemodialysis (HD) patients. Vitamin D exerts its effects through the vitamin D receptor (VDR) that is coded for by a gene showing several polymorphisms that, in turn, are associated with a variety of diseases and differential responses to vitamin D. In this study, we evaluated the association between 4 VDR polymorphisms (ie, those identified by the restriction enzymes BsmI, ApaI, TaqI, and FokI) and iron indices (serum iron, transferrin, transferrin saturation, and ferritin) in 88 hemodialysis patients routinely treated with vitamin D. The absence or presence of the BsmI, ApaI, TaqI, and FokI restriction sites were denominated B and b, A and a, T and t, F and f, respectively. Our results show that in HD patients with transferrin saturation <20%, the F allele was more frequent than in HD patients with transferrin saturation >20% (P = .03). This relationship may provide a link between VDR alleles and iron and nutritional markers, which are highly predictive variables of cardiovascular morbidity and mortality in hemodialysis patients.

Nutritional-inflammation status and resistance to erythropoietin therapy in haemodialysis patients.

BACKGROUND: Chronic kidney disease patients who are resistant to erythropoietin (EPO) treatment may suffer from malnutrition and/or inflammation. METHODS: In a cross-sectional study of haemodialysis patients, we investigated the relationship between the natural logarithm of the weekly EPO dose normalized for post-dialysis body weight and outcome measures of nutrition and/or inflammation [BMI, albumin and C reactive protein (CRP)] by means of multiple linear regression analysis. On the basis of the decile distribution of weekly EPO doses, we also evaluated four groups of patients: untreated, hyper-responders, normo-responders and hypo-responders. RESULTS: Six hundred and seventy-seven adult haemodialysis patients were recruited from five Italian centres. BMI and albumin were lower in the hypo-responders than in the other groups (21.3+/-3.8 vs 24.4+/-4.7 kg/m(2), P<0.001; and 3.8+/-0.6 vs 4.1+/-0.4 g/dl, P<0.001), whereas the median CRP level was higher (1.9 vs 0.8 mg/dl, P = 0.004). The median weekly EPO dose ranged from 30 IU/kg/week in the hyper-responsive group to 263 IU/kg/week in the hypo-responsive group. Transferrin saturation linearly decreased from the hyper- to hypo-responsive group (37+/-15 to 25+/-10%, P = 0.003), without any differences in transferrin levels. Ferritin levels were lower in the hypo-responsive than in the other patients (median 318 vs 445 ng/ml, P = 0.01). At multiple linear regression analysis, haemoglobin, BMI, albumin, CRP and serum iron levels were independently associated with the natural logarithm of the weekly EPO dose (R(2) = 0.22). CONCLUSIONS: Our findings support a clear association between EPO responsiveness and nutritional and inflammation variables in haemodialysis patients; iron deficiency is still a major cause of hypo-responsiveness.

Pure red-cell aplasia in a peritoneal dialysis patient with HCV-related cryoglobulinemia in the absence of neutralizing antierythropoietin antibodies.

Pure red-cell aplasia (PRCA) in recombinant human erythropoietin (rHuEpo) treated patients is a matter of growing concern. In most cases, neutralizing anti-EPO antibodies have been detected in patient serum and held responsible for the development of PRCA. We describe a 68-year-old white woman suffering from HCV-related cryoglobulinemia and chronic kidney disease on renal replacement therapy with peritoneal dialysis. Five months after the introduction of epoetin-b therapy she developed a PRCA, as shown by the bone marrow aspirate. Cryocrit rose from 5% to 15% at this time, reticulocyte count fell, while white blood cells and platelets remained within normal values. Epoetin-b therapy was discontinued and steroid treatment was started. The test for anti-erythropoietin antibodies was negative. Hemoglobin and reticulocytes progressively rose and steroid therapy was tapered and eventually stopped, when the cryocrit was 3%. We propose that a relapse in the HCV-related cryoglobulinemia might be held responsible for the erythropoietic marrow failure.